Novel, Prostate-Specific Gene for Diagnosis, Prognosis and Management of Prostate Cancer

Abstract

Disclosed are nucleic acid and amino acid sequences encoded by a novel, prostate specific gene (UC41) and diagnostic techniques for the detection of human prostate cancer utilizing such nucleic acid and amino acid sequences. Genetic probes and methods useful in monitoring the progression and diagnosis of prostate cancer are described. Methods of treatment for prostate cancer utilizing antisense constructs or antibodies specific for UC41 gene products are also described.

1 - 23 . (canceled) 
     
     
         23 . A method of treating a subject with prostate cancer, comprising the steps of:
 (a) obtaining a biological sample from a subject with prostate cancer;   (b) screening said sample for the expression of a prostate cancer marker using an antibody that binds immunologically to a polypeptide comprising SEQ ID NO:2 or SEQ ID NO:5; and   (c) administering an effective amount of said antibody to said subject.   
     
     
         24 . A method of treating a subject with prostate cancer, comprising the steps of:
 (a) obtaining a biological sample from a subject with prostate cancer;   (b) screening said sample for the expression of a prostate cancer marker;   (c) providing an antisense DNA molecule that encodes an RNA molecule that binds to a polynucleotide comprising SEQ ID NOs: 1, wherein said antisense DNA molecule comprises a vector containing human regulatory elements for the production of said RNA molecule; and   (d) administering an effective amount of said vector to said subject.   
     
     
         25 - 27 . (canceled) 
     
     
         28 . A method for detecting prostate cancer cells in a biological sample, comprising the following steps:
 (a) obtaining a biological sample from a subject;   (b) providing an antibody that binds immunologically to a polypeptide comprising SEQ ID NO:2 or SEQ ID NO:5;   (c) contacting the biological sample with the antibody; and   (d) detecting the antibody bound to the biological sample, wherein detection of the antibody to the biological sample indicates the presence of prostate cancer cells in the biological sample.   
     
     
         29 - 32 . (canceled) 
     
     
         33 . The method of  claim 24 , wherein said antisense DNA molecule encodes a full length complementary sequence to SEQ ID NO:1 or a portion of SEQ ID NO:1 comprising at least 8 contiguous base pairs in length. 
     
     
         34 . The method of  claim 23 , wherein said antibody is in the form of a single chain antibody. 
     
     
         35 . The method of  claim 34 , wherein said administering step comprises providing an expression vector that encodes said single-chain antibody. 
     
     
         36 . The method of  claim 28 , wherein the antibody comprises a polyclonal antibody or a monoclonal antibody. 
     
     
         37 . The method of  claim 28 , wherein the antibody comprises an antibody fragment. 
     
     
         38 . The method of  claim 28 , wherein the antibody is a monoclonal antibody and is conjugated to a detectable moiety. 
     
     
         39 . The method of  claim 38 , wherein the detectable moiety comprises a radioactive, fluorescent, biological or enzymatic moiety. 
     
     
         40 . The method of  claim 39 , wherein the radioactive moiety is a radionuclide. 
     
     
         41 . The method of  claim 28 , further comprising separating the antibody bound to the biological sample of step (c) from unbound antibody. 
     
     
         42 . The method of  claim 28 , wherein the antibody bound to the biological sample is detected by an enzyme-linked immunosorbent assay (ELISA), a radioimmunoassay (RIA), a Western blot assay, a dot blotting assay, a slot blot assay, a fluorescence activated cell sorting (FACS) assay or an immunohistochemistry assay. 
     
     
         43 . The method of  claim 28 , wherein the biological sample comprises a sample that is suspected of containing a polypeptide comprising SEQ ID NO:2 or SEQ ID NO:5. 
     
     
         44 . The method of  claim 28 , wherein the biological sample comprises normal prostate cells, primary prostate cancer cells, metastatic prostate cancer cells or a combination thereof 
     
     
         45 . The method of  claim 28 , wherein the biological sample comprises a sample that is suspected of containing prostate cancer cells. 
     
     
         46 . The method of  claim 45 , wherein the biological sample comprises prostate tissue , lymph node tissue , spleen tissue, skin tissue, organ tissue, bone marrow tissue, or isolated cells thereof. 
     
     
         47 . The method of  claim 28 , wherein the biological sample comprises prostate tissue, lymph node tissue or a biological fluid that comes into contact with prostate tissue or lymph node tissue. 
     
     
         48 . The method of  claim 28 , wherein the biological sample comprises a fresh-frozen paraffin-embedded tissue blocks or a formalin-fixed paraffin-embedded tissue block. 
     
     
         49 . The method of  claim 28 , further comprising the steps of:
 (e) quantifying the amount of a prostate cancer marker in the biological sample using the antibody that binds immunologically to a polypeptide comprising SEQ ID NO:2 or SEQ ID NO:5; and   (f) comparing the amount of the prostate cancer marker in the biological sample of step (e) to the amount of the prostate cancer marker in a normal reference sample,   wherein an increased amount of the prostate cancer marker in the biological sample of step (e) relative to the amount of the prostate cancer marker in the normal reference sample is indicative of prostate cancer cells in the biological sample of step (e).   
     
     
         50 . The method of  claim 28 , further comprising determining the prognosis of a subject having prostate cancer, wherein the biological sample is obtained from said subject, by quantifying the amount of the prostate cancer marker in the biological sample bound by the antibody that binds immunologically to a polypeptide comprising SEQ ID NO:2 or SEQ ID NO:5, wherein an amount of the prostate cancer marker above a cut-off amount corresponds to a relatively worse prognosis for the subject as compared to the prognosis corresponding to prostate marker levels below the cut-off amount. 
     
     
         51 . The method of  claim 28 , further comprising determining the diagnosis of a subject suspected of having prostate cancer, wherein the biological sample is obtained from said subject, by quantifying the amount of the prostate cancer marker in the biological sample bound by the antibody that binds immunologically to a polypeptide comprising SEQ ID NO:2 or SEQ ID NO:5, wherein an increased amount of the prostate cancer marker relative to a cut-off amount corresponds to a diagnosis of prostate cancer in the subject. 
     
     
         52 . A method for detecting prostate cancer cells in a subject comprising the following steps:
 (a) administering an imaging-effective amount of a detectably-labeled antibody that binds immunologically to a polypeptide comprising SEQ ID NO:2 or SEQ ID NO:5 and a pharmaceutically effective carrier to a subject;   (b) detecting the antibody that is bound to prostate cancer cells in the subject.   
     
     
         53 . The method of  claim 52 , wherein the antibody bound to the prostate cancer cells in the subject is detected by a radio-imaging assay. 
     
     
         54 . The method of  claim 52 , wherein the detectably-labeled antibody comprises an antibody conjugated to a radioactive moiety. 
     
     
         55 . The method of  claim 54 , wherein the radioactive moiety is a radionuclide. 
     
     
         56 . A method of determining the ability of a candidate substance to inhibit expression of the UC41 gene, the method comprising the steps of:
 (a) providing at least one UC41-expressing prostate cell;   (b) contacting the at least one UC41-expressing prostate cell with a candidate substance;   (c) measuring the level of UC41 expression in the at least one UC41-expressing prostate cell; and   (d) comparing the level of UC41 expression in the at least one UC41-expressing prostate cell of step (c) with the level of UC41 expression measured in at least one UC41-expressing prostate cell in the absence of the candidate substance, wherein a candidate substance inhibits expression of the UC41 gene when the level of UC41 expression in the at least one UC41-expressing prostate cell of step (c) is less than the level of UC41 expression measured in the at least one UC41-expressing prostate cell in the absence of the candidate substance.   
     
     
         57 . The method of  claim 56 , wherein UC41 expression is measured by detection of expression of a polynucleotide that hybridizes to a polynucleotide comprising the sequence set forth in SEQ ID NOs. 1, 3 or 4. 
     
     
         58 . The method of any one of  claims 56 , wherein the at least one UC41 expressing prostate cell is provided as an adherent cell on a culture dish, as part of an alginate biomatrix, or in a suspension culture. 
     
     
         59 . The method of  claim 56 , wherein the level of UC41 expression is measured by a Northern blot assay or a slot blot assay. 
     
     
         60 . The method of  claim 57 , wherein the level of UC41 expression is measured by an enzyme-linked immunosorbent assay (ELISA), a radioimmunoassay (RIA), a Western blot assay, a dot blotting assay, a fluorescence activated cell sorting (FACS) assay or an immunohistochemistry assay. 
     
     
         61 . The method of  claim 56 , wherein the at least one prostate cancer cell comprises a biological sample from a subject with prostate cancer. 
     
     
         62 . The method of  claim 56 , wherein the at least one UC41-expressing prostate cancer cell is in a subject with prostate cancer. 
     
     
         63 . The method of  claim 62 , wherein the level of UC41 expression is measured by a radio-imaging assay. 
     
     
         64 . The method of  claim 63 , wherein the radio-imaging assay comprises the steps of:
 (a) administering to the subject an imaging-effective amount of a detectably-labeled antibody that binds immunologically to a polypeptide comprising SEQ ID NO:2 or SEQ ID NO:5 and a pharmaceutically effective carrier;   (b) detecting the antibody bound to prostate cancer cells in the subject.   
     
     
         65 . The method of  claim 64 , wherein the detectably-labeled antibody comprises an antibody conjugated to a radioactive moiety. 
     
     
         66 . The method of  claim 65 , wherein the radioactive moiety is a radionuclide. 
     
     
         67 . The use of a prostate cell which expresses a UC41 gene encoding the polynucleotide sequence set forth in SEQ NOs. 1, 3 or 4 to screen for modulators of UC41 expression. 
     
     
         68 . The use of  claim 67 , wherein the UC41-expressing prostate cell is provided as an adherent cell on a culture dish, as part of an alginate biomatrix, or in a suspension culture.